9YXW
Crystal structure of HCoV-HKU1 RBD bound by H501-008 Fab
Summary for 9YXW
| Entry DOI | 10.2210/pdb9yxw/pdb |
| Descriptor | Spike protein S1, H501-008 Fab heavy chain, H501-008 Fab light chain, ... (4 entities in total) |
| Functional Keywords | hcov-hku1, coronavirus, antibody, fab, viral protein |
| Biological source | Human coronavirus HKU1 More |
| Total number of polymer chains | 3 |
| Total formula weight | 82932.59 |
| Authors | |
| Primary citation | Wang, L.,Joseph, J.,Vasquez, S.,Wrapp, D.,Sheahan, T.P.,Dzuvor, C.K.O.,Rosen, O.,Kirchdoerfer, R.N.,Abiona, O.M.,Hammond, C.,Shi, W.,Moak, S.P.,Kong, W.P.,Zhang, Y.,Eso, M.R.,Brown, A.J.,Ward, A.B.,Baric, R.,McLellan, J.S.,Pierson, T.C.,Mascola, J.,Graham, B.S.,Yassine, H.M.,Barnes, C.O.,Corbett-Helaire, K.S. Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site. Biorxiv, 2025 Cited by PubMed Abstract: Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ~30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, little is known about HCoV-HKU1's antigenic landscape. Thus, we characterized key interactions between HCoV-HKU1 spike (S) with monoclonal antibodies (mAbs) isolated from pre-pandemic HCoV-HKU1 convalescent PBMCs. We isolated 14 mAbs, which bound distinct S regions: receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Structural and functional studies revealed three groups of RBD-specific mAbs targeting diverse footprints within and around the TMPRSS2 receptor binding site, exemplified by: (1) The most potently neutralizing mAb, H501-022 (IC = 0.01 μg/mL), which recognizes the TMPRSS2 binding motif, thereby blocking receptor engagement; (2) mAb H501-008 (IC = 0.05 μg/mL) that binds a conserved, cross-reactive epitope outside of the TMPRSS2 binding site that is shared with HCoV-OC43; and (3) H501-018 (IC = 0.28 μg/mL) that recognizes both "up" and "down" RBD conformations at a distinct, non-overlapping site outside of the TMPRSS2 binding motif, distinguishing itself from H501-022 and H501-008, which bind exclusively to the "up" RBD conformation. These mAbs represent the first type-specific HCoV-HKU1 mAbs isolated from a convalescent donor. Our findings provide molecular insight into HCoV-HKU1 antibody recognition and neutralization mechanisms, importantly highlighting antigenic differences comparing HCoVs and pandemic CoVs - a critical step towards advancing universal CoV vaccine design. PubMed: 41279056DOI: 10.1101/2025.10.29.685445 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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